Process of preparing vitamin d



April 18, 1.933- E. H. REERINK El AL 399949751 PROCESS OF PREPARING VITAMIN D Filed June 9, 1930 Adar/z q],

Patented Apr. 18, 1933 UNITED. STATES PATENT OFFICE nnennnr mm annairrx AND AART van win; or nmnnovnn, NETHERLANDS;

ASSIGNORS TON. V. PHILIPS GLOEILAMPENFABRIEKEN, OF EIINDEOYEN', NETHER-" LANDS PROCESS OF PREPARING VITAMIN 1) Application filed June 9, 1930, Serial No. 460,066, and in the Netherlands July 20, 19 29.

This invention relates to an improved process of preparing vitamin D. 7 It is well known that ergosterol on being subjected to radiation by" ultra-violet light is converted into vitamin D, a product which has proved to be of great value as a remedy against rachitis. Y

The invention has reference to a process of preparin vitamin D in this manner and 10 has for its 0 ject to increase the efliciency of the radiation.

The unsatisfactory results obtained heretofore have been imputed inter alia to the action exercised by the light used for radiation on the vitamin D produced, since the latter is partially decomposed by ultra-violet light into products which hereinafter will be referred to as demolition products. It has been proposed to avoid this decomposition into alia by weakening a definite region of the ultraviolet spectrum which was believed to bring about the said decomposition and to be the absorption zone of vitamin D, and weakening it to such an extent that according to the prevailing opinion it caused no longer any serious decomposition of vitamin D 1nto demolition products.

In contradistinction to existing theories it has now been found that the part of the spectrum to which the decomposition ofvitamin D wasimputed is not to any extent more active in this respect than the remaining part of the ultra-violet spectrum. It is therefore comprehensible that a satisfactory improvement was not obtained by means of the weakening operation resorted to. There is however a further reason why the methods ofoperation hitherto'known were not so effective as the process hereinafter described,isince it has now been found that on ergosterol being subjected to radiation not only vitamin D but also a number of products are formed which were unknown heretofore. There substances, which in distinction from the decomposition products of the vita min D produced will be referred to hereinafter as by-products, are comparatively valueless as they practically do not exercise any antirachitic action and are to be regarded therefore as impurities of the vitamin D produced;

' In addition it has been found that the ultraviolet spectrum is possessed of zones in which the light rays are essentially active in.

According to the invention a hitherto unknown useful effect is obtained by using for the radiation to which ergosterol is to be subjected ultraviolet light while filtering out wavelengths of the order of 27 0 m or less and discontinuing such radiation before more than approximately of the ergosterol has been transformed. Thus the formation of any demolition products in such amountas to affect the purity of the vitamin D to a serious extent is avoided. Further, it has been found that it is desirable that the light used should be substantially devoid of wavelengthsgreater than 300 11111.; however, it is obvious that any part of the spectrum which has no effect upon the ergosterol need not be filtered out.

The process according to the invention may be carried out by means of a filter absorbing the undesired rays and letting through as far as possible the vitamin D producing rays orby using a light source. that emits no rays exercising an undue action on ergosterol. Generally, a suflicient result may be obtained by means of light emitted from a suitable light source, say a mercury arc lamp, said light being caused to pass through a filter formed by a quantity of preferably dilute benzene. As acondition actinic rays which are of 110 essential importance in connection with the formation of vitamin D should be adsorbed by the filter to such a great extent that practically they do not act on ergosterol, and the remaining ultra-violet rays should be transmitted in a possibly undisturbed man ner. Obviously, the thickness of the filterergosterol in a comparatively intense manner,

but particularly if powerful intensities occur in this region a deleterious effect is also to be attributed to such rays. It is therefore preferable that light having a wave length below 282 m should not be used, although the reaction will consequently be carried out in a slightly less rapid manner.

For the purpose above described a filter containing paraxylol is quite adapted for use, particularly in conjunction with anelectric discharge in bismuth, or mercury vapour or with a similar light source.

The duration of the radiation is dependent upon the intensity of the light source, upon the degree to which the rays are absorbed and upon the quantity of the preparation to be treated. The radiation mustnot be continued until all the ergosterol has been trans- "formed, because'by and by part of the vitamin D produced is decomposed into demolition products so that the efiiciency is lowered. For that reason, the treatment is terminated before more than approximately of the ergosterol has been transformed. In the case of using a mercury arc lamp and a filter which is not too strong, a radiation for 10 minutes may sufilce for the treatment of a quantity of ergosterol of about 1 milligram.

When subjected to the radiation the ergosterolmay be in a solid state, but alternatively it may be dissolved in ether, hexane or other means for this purpose.

The invention will be more clearly under stood by reference to the accompanying drawing in which Figure 1 shows diagrammatically the arrangement of the devices used, and

Figure 2 is a different projection of one of these devices.

The ultraviolet light is radiated by a mercury vapour lamp ,1 comprising a .mercury electrode 2 and a solid electrode The current -is supplied to the tube from a trans former 4 with the interposition of a series resistance 5. The wall of the tube is of quartz which is transparent in a substantially uniform manner to the light radiated by the mercury arcs This light strikes a bulb 6 in which the substance to be subjected to radiation is enclosed. .The light rays pass, however, through an interposed bulb 7 the wall of which is of quartz similarly to that of 6. The vessel 7 is filled with a liquid, for example a benzene solution, which arrests light having a wavelength shorter than 270 me, or with still greater advantage a substance that absorbs rays up to 282 m but which on the contrary lets through longer wavelengths in a substantially undisturbed manner. The bulb 6 contains a solution of ergosterol in ether, hexane or the like. This vessel has sealed to it tubes 8 and 9 through which the liquid can be delivered or discharged, a continuous production being thus ensured. The speed at which the liquid flows through the vessel 6 may be controlled so as to ensure a maximum antirachitic action of the preparation subjected to radiation.

Figure 2 is a sectional view of the bulb 7 which is formed by a small cylinder of quartz 10 sealed at both ends by small plates 11 which are also of quartz. The c linder has sealed to it tubes 12 and 13 whic permit of the vessel being exhausted and the liquid being introduced. After the vessel has been filled, these tubes are sealed off. The remaining parts of the tubes may serve for supports.

. What we claim is 1. In a process of preparing a material containing vitamin D, the steps comprising subjecting ergosterol to radiation by artificially produced ultraviolet light while filtering out light of wave lengths of the order of 270 m or less, and discontinuing such radiation before more than approximately 60% of the ergosterol has been transformed.

2. In a process of preparing a maternal containing vitamin subjecting ergosterol to radiation by artificially produced ultraviolet light while filtering out light of wave lengths shorter than 282 m and discontinuingsuch radiation before more than approximately 60% of the ergosterol has been transformed.

3. In a process of preparing a maternal containing vitamin D, the steps comprising subjecting ergosterol to radiation by artificially produced ultraviolet light while filtering out light of wave lengths of the order of 270 m or less and substantially all of the light of wave lengths greater than 300 111p. and discontinuing such radiatlon before more than approximately 60% of the ergosterol has been transformed.

4. In a process of preparing a material containing vitamin D, the steps comprising subjecting ergosterol to radiation by artificially produced ultraviolet light while filtering'out light of wave lengths shorter than 282 m and substantially all of the D, the steps comprising light of wave lengths greater than 300 m and discontinuing such radiation before more than approximately 60% of the ergosterol has been transformed. 5. In a process of preparing a material containing vitamin D, the steps comprising subjecting ergosterol to radiation by light of wave length substantially limitedto the hand between 282 my and 300 m;:., and dis-- 1 continuing such radiation before more than approximately 60%. of the ergosterol has been transformed.

In testimony whereof we have signed our 1 names to this specification. 15. ENGBERT HARMEN REERINK.

AART VAN WIJK. 

